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MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells

The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is...

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Autores principales: Yang, Ting, He, Wanming, Cui, Fei, Xia, Jianling, Zhou, Rui, Wu, Zhenzhen, Zhao, Yang, Shi, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951273/
https://www.ncbi.nlm.nih.gov/pubmed/26919111
http://dx.doi.org/10.18632/oncotarget.7634
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author Yang, Ting
He, Wanming
Cui, Fei
Xia, Jianling
Zhou, Rui
Wu, Zhenzhen
Zhao, Yang
Shi, Min
author_facet Yang, Ting
He, Wanming
Cui, Fei
Xia, Jianling
Zhou, Rui
Wu, Zhenzhen
Zhao, Yang
Shi, Min
author_sort Yang, Ting
collection PubMed
description The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is unclear how MACC1 activity is regulated in GC. In this study, we demonstrated that ACh acts via M3Rs to promote GC cell invasion and migration as well as expression of several markers of epithelial-mesenchymal transition (EMT). The M3R antagonist darifenacin inhibited GC cell activity in both the presence and absence of exogenous ACh, suggesting GC cells secrete endogenous ACh, which then acts in an autocrine fashion to promote GC cell migration/invasion. ACh up-regulated MACC1 in GC cells, and MACC1 knockdown using siRNA attenuated the effects of ACh on GC cells. AMP-activated protein kinase (AMPK) served as an intermediate signal between ACh and MACC1. These findings suggest that ACh acts via a M3R/AMPK/MACC1 signaling pathway to promote GC cell invasion/migration, which provides insight into the mechanisms underlying GC growth and metastasis and may shed light on new targets for GC treatment.
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spelling pubmed-49512732016-07-21 MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells Yang, Ting He, Wanming Cui, Fei Xia, Jianling Zhou, Rui Wu, Zhenzhen Zhao, Yang Shi, Min Oncotarget Research Paper The neurotransmitter acetylcholine (ACh) promotes the growth and metastasis of several cancers via its M3 muscarinic receptor (M3R). Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that is overexpressed in gastric cancer (GC) and plays an important role in GC progression, though it is unclear how MACC1 activity is regulated in GC. In this study, we demonstrated that ACh acts via M3Rs to promote GC cell invasion and migration as well as expression of several markers of epithelial-mesenchymal transition (EMT). The M3R antagonist darifenacin inhibited GC cell activity in both the presence and absence of exogenous ACh, suggesting GC cells secrete endogenous ACh, which then acts in an autocrine fashion to promote GC cell migration/invasion. ACh up-regulated MACC1 in GC cells, and MACC1 knockdown using siRNA attenuated the effects of ACh on GC cells. AMP-activated protein kinase (AMPK) served as an intermediate signal between ACh and MACC1. These findings suggest that ACh acts via a M3R/AMPK/MACC1 signaling pathway to promote GC cell invasion/migration, which provides insight into the mechanisms underlying GC growth and metastasis and may shed light on new targets for GC treatment. Impact Journals LLC 2016-02-23 /pmc/articles/PMC4951273/ /pubmed/26919111 http://dx.doi.org/10.18632/oncotarget.7634 Text en Copyright: © 2016 Yang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yang, Ting
He, Wanming
Cui, Fei
Xia, Jianling
Zhou, Rui
Wu, Zhenzhen
Zhao, Yang
Shi, Min
MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
title MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
title_full MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
title_fullStr MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
title_full_unstemmed MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
title_short MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
title_sort macc1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951273/
https://www.ncbi.nlm.nih.gov/pubmed/26919111
http://dx.doi.org/10.18632/oncotarget.7634
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